The long range objective of this project is to identify and understand the mechanism or mechanisms which regulate the dramatic physiological adaptations associated with pregnancy at a systems level in humans and how these adaptive responses are altered by gestational diabetes. These studies are designed to examine the hypotheses that the adaptations in cardiopulmonary and metabolism in the mother, occur very early in gestation at a time when the fetus is small and has just completed the organ differentiation and that these multiple systems adaptations are to a variable degree permanent. Specifically, these studies will examine and quantify the longitudinal first trimester alterations in a group of specific, selected morphometric, metabolic and cardiopulmonary functions, and correlate these changes with those in hormonal profile as an initial approach to examine a potential central hormonal regulatory mechanism. Serial, longitudinal changes in these parameters will be quantified in a group of women through pregnancy and at inter- vals postpartum. The same specific parameters will be measured longitudinally in a cohort of nonpregnant women undergoing ovulation induction, in order to examine the hormonal mechanism involved. The cardiopulmonary responses will be measured in combination with studies of glucose production, utilization, oxidation using stable isotopic tracers and respiratory calorimetry. These studies will be done in the basal resting state and the responses to meal and exercise will be quantified. These studies are significant in that they will allow us to obtain new information that will form the data base necessary to understand the central regulatory mechanisms involved in the metabolic alterations and physiological adaptations in human pregnancy.